Nitroaromatics, carbonylation

Carbonylation of Nitroaromatics Carbonylation of nitroaro-matics to isocyanates... 

General evidence for that kind of mechanism comes from ab initio theoretical calculations performed on a related platinum complex [3, 44] and from the reactivity of four- and five-membered heterometallacyles [45] structurally close to some of the intermediates in postulated mechanisms (e.g.. Scheme 3). Moreover, related metallacycles have often been isolated from the reaction medium after nitroaromatic carbonylation, indicating that such species can easily be generated under typical carbonylation conditions [46, 47]. 

The synthesis and characterization of a family of metallacyclic complexes (147)- (150) of Pd, were reported. The complexes were isolated during the catalytic carbonylation of nitroaromatics... 

In the [Ru(CO)3(dppe)] catalysed carbonylation of para-nitrotoluene (Eq. (6)) HP IR spectroscopy indicated conversion of the Ru(0) complex into an oxidised species with v(CO) bands at higher frequency [41]. A mechanism involving single-electron-transfer from the nitroaromatic to the Ru complex was proposed. 

Hydrolysis of the ester forms adipic acid, used to manufacture nylon—6. Carbonylations of nitroaromatics are used to synthesize an array of products including amines, carbamates, isocyanates, ureas and azo compounds. These reactions are catalyzed by iron, ruthenium, rhodium and palladium complexes. For example, carhonylation of nitrobenzene in the presence of methanol produces a carbamate ... 

Wang et report the carbonylation of nitroaromatics with aromatic amines in a catalytic system containing elemental sulfur in an ionic liquid, Scheme 3. 

Gokel for reducible quinone (25, 26) and nitroaromatic (32, 33) lariat crown ethers with alkali metal guest cations discussed earlier. Support for the latter effect comes from the related ligand system (81), containing no amide carbonyl groups, and electrochemical results revealing... 

Carbonylation of methanol and nitroaromatics, hydroformylation of olefins and alcohol homologation were among the principal reactions aimed at producing high added value molecules. 

The presence of any of several functional groups is likely to impart photolability to drug molecules. These include carbonyl (C=0), nitroaromatic, -N-oxide, -alkene (C=C), aryl chloride, weak C-H and O-H bonds, sulfides, and polyenes. Some of these functional groups impart photolability as a result of their chromophoric properties (e.g., carbonyl) and some of them impart photolability by virtue of their weak covalent bonds, (e.g., O-H bonds). A list of several common bonds and their respective bond energies (E ) and the corresponding wavelengths ( ) are presented in Table 1. 

Carbonyl group Nitroaromatic group A-oxide function Carbon-carbon double bond Aryl halide... 

Although it is difficult to predict which drugs are likely to be prone to photodegradation, there are certain chemical functions that are expected to introduce photoreactivity, including carbonyl, nitroaromatic and N-oxide functions, aryl halides, alkenes, polyenes and sulfides. The mechanisms of photodegradation are of such complexity as to have been fully elucidated in only a few cases. We will consider two examples - chlorpromazine and ketoprofen. 

A base reaction is also made responsible for the palladium(II)-catalyzed reductive carbonylation of nitroaromatics to isocyanates. Carhon monoxide affects the reduction step Pd ---> Pd° in protic media [14] according to eq. (9). The consecutive... 

The ideal method of reductive carbonylation of nitroaromatics would employ synthesis gas according to eq. (13) CO as a carbonylation reagent is cheaper in the form of syngas than pure CO, but it is more expensive as a reducing agent (eq. (8)) than hydrogen. Unfortunately, there is as yet no catalyst for the overall conversion of eq. (13) only the stepwise reduction works cata-lytically. 

Reductive carbonylation of nitro compounds, especially nitroaromatic compounds according to eq. (1), has been the subject of thorough industrial research starting in 1962 and continuing until the beginning of the 1990s due to the demand for a new, phosgene-free method for the production of isocyanates [1] and the discussions on the chlorine cycle in industry. 

Numerous patents [3, 11-13] and other publications [3, 14-16] describe the direct carbonylation of nitroaromatic compounds to isocyanates or alternatively a modified carbonylation to urethanes in the presence of alcohol, followed by a thermal transformation to isocyanates [4, 17-19] (eq. (2)). 

In the first reported direct A -carbonylation of nitroaromatics to isocyanates, simple Pd- or Rh-based systems were used to catalyze the reaction of aromatic mononitro compounds with carbon monoxide [11, 12]. Later, it became possible to work without the drastic reaction conditions that had been required initially, by using Lewis acid co-catalysts [13], Various catalysts and catalyst mixtures, normally based on Ru, Rh, or Pd complexes with co-catalysts, were described in numerous patents and publications [1, 3, 14—16], The careful choice of the composition of the triad consisting of metal salt, co-catalysts and ligand (preferably aromatic amines) led to efficient catalyst systems [14a-e] for the direct reductive carbonylation process. A quite active Pd-phenanthroline-H system with noncoordinating carboxylic acids such as 2,4,6-trimethlybenzoic acid as proton source is worth mentioning [14 d]. 

Summarizing, from the investigations in this field it can be concluded that from an industrial viewpoint the direct carbonylation of nitroaromatics to isocyanates represents no economically feasible alternative, for the conventional phosgenation process, for the following reasons ... 

In an early publication [16] the carbonylation of nitroaromatics was described as a stepwise deoxygenation of the nitro group, generating an excited singlet nitrene (probably stabilized by coordination on a metal center). Based on this description, the formation of a metal-imido intermediate was usually assumed in most of the proposed mechanisms until the mid-1980s [5, 34-38]. 

Despite several experimental facts [3] rendering a transient metal-imido species a likely source for many products of the carbonylation reaction, its role as an actual intermediate in the catalytic transformation of simple nitroaromatic substrates has never been proven. Accordingly, a type-5 mechanism (Scheme 3, involving no such intermediate) could also be operative for the formation of isocyanate. In this case, an imido complex could also be generated by a parallel minor pathway... 

Conceptually, the indirect carbonylation of nitroaromatics can be pictured as a direct carbonylation reaction, followed by a scavenger reaction of the highly reactive intermediate isocyanate by the alcohol in a subsequent step before by-product formation comes into play. The latter is known to occur spontaneously at ambient temperature [48,49] and is catalyzed efficiently by many compounds having... 

J. Z. Chen, G. Ling, S. Lu, Synthesis of N-phenyl-N-pyrimidylurea derivatives by selenium-or selenium dioxide-catalyzed reductive carbonylation of nitroaromatics, Eur. J. Org. Chem. 17... 

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